crossing96/oncoscreening huggingface dataset:
Optimizing pharmacokinetics of intravesical chemotherapy for bladder cancer.	Non-muscle-invasive bladder cancer (NMIBC) remains one of the most common malignancies and is associated with considerable treatment costs. Patients with intermediate-risk or high-risk disease can be treated with intravesical BCG, but many of these patients will experience tumour recurrence, despite adequate treatment. Standard of care in these patients is radical cystectomy with urinary diversion, but this approach is associated with considerable morbidity and lifestyle modification. As an alternative, perioperative intravesical chemotherapy is recommended for low-risk papillary NMIBC, and induction intravesical chemotherapy is an option for patients with intermediate-risk NMIBC and BCG-unresponsive NMIBC. However, poor pharmaceutical absorption and drug washout during normal voiding can limit sustained drug concentrations in the urothelium, which reduces efficacy, and small-molecule chemotherapeutic agents can be absorbed through the urothelium into the bloodstream, leading to systemic adverse effects. Several novel drug delivery methods - including hyperthermia, mechanical sustained released devices and nanoparticle drug conjugation - have been developed to overcome these limitations. These novel methods have the potential to be combined with established chemotherapeutic agents to change the paradigm of NMIBC treatment.	bladder
Use of Toceranib Phosphate in the Treatment of Canine Bladder Tumors: 37 Cases.	Transitional cell carcinoma (TCC) is a locally aggressive tumor in dogs with low-to-moderate responses to traditional chemotherapeutic agents. Toceranib (TOC) phosphate represents a novel agent for the treatment of canine TCC. Thirty-seven dogs were identified who had received TOC for bladder tumor treatment. The TOC was generally well tolerated, although 56% of dogs had progression of azotemia while receiving TOC. A partial response to TOC was observed in 6.7% of dogs, and 80% of dogs had stable disease for a median duration of 128.5 days. Median time to progression was 96 days, and median survival time after the start of TOC was 149 days. There were no significant variables influencing time to progression or survival time in this group of dogs. This retrospective study suggests that TOC may be useful for the treatment of TCC. However, careful monitoring of renal function is recommended in patients with bladder tumors receiving TOC.	bladder
Upregulation of neurotrophins and transforming growth factor-β expression in the bladder may lead to nerve hyperplasia and fibrosis in patients with severe ketamine-associated cystitis.	AIMS: To investigate the mechanism of bladder nerve hyperplasia and fibrosis in the patients with ketamine-associated cystitis (KC). METHODS: Sixteen patients with severe KC, six patients with mild KC, and five patients with localized invasive bladder cancer served as control patients. Bladder mucosa specimens were taken during the operations, and the specimens were stained for nerve growth factor (NGF) and S-100 to evaluated nerve hyperplasia. The quantitative Western blot analysis was performed for NGF, brain-derived neurotrophic factor (BDNF), growth-associated protein 43 (GAP-43), tropomyosin receptor kinase A and B (TrkA and TrkB), transforming growth factor-β (TGF-β), phosphorylated extracellular signal-regulated kinases (p-ERK), protein kinase B (p-Akt), and glycogen synthase kinase 3β (p-GSK-3β). RESULTS: The results demonstrated diffuse NGF expression in KC bladder epithelium, lamina propria, and muscle. The GAP-43, NGF, BDNF, TrkA, TGF-β, p-ERK, P-AKT, and p-GSK-3β expression in the bladder mucosa specimens of patients with severe KC was significantly higher than in patients with mild KC and control patients. Expression of neurotrophins was significantly correlated with bladder capacity and pain. NGF and BDNF expression were significantly higher in the KC bladder specimens with strongly positive S-100 staining. TGF-β expression in the bladder specimens was significantly correlated with neurotrophins, p-ERK, P-AKT, and p-GSK-3β levels. CONCLUSION: Our findings indicate upregulation of neurotrophins, TGF-β, and activation of the cell proliferation kinases plays an important role in nerve hyperplasia and fibrosis mechanisms in severe KC bladders. The neurotrophins and TGF-β interact as cause and effect, leading to bladder hypersensitivity and fibrosis in severe KC.	bladder
Amyloidosis of the bladder and association with urothelial carcinoma: report of 29 cases.	The association of amyloidosis with certain neoplastic processes is well known. Amyloid uncommonly occurs in relationship with other epithelial neoplasms including urothelial carcinoma. Herein, we report 29 cases of amyloidosis in the bladder, 14 of which were found in relationship to urothelial carcinoma. With institutional review board approval. We searched pathology archives for cases of amyloidosis in the bladder. Clinical, laboratory, and surgical pathology records were reviewed, and data were recorded for all cases. Diagnosis of amyloid was made by Congo red stain showing apple-green birefringence on polarization microscopy and special studies in some cases. Twenty-nine cases of amyloid were identified in bladder specimens. Presentation as a mass lesion was the most common (n = 18). Immunohistochemical subtyping done in 17 cases showed transthyretin-type (n = 10), AL (n = 3), AA (n = 1), amyloid P (n = 1), and undetermined (n = 2) types of amyloid. Eighteen (62%) cases were classified as localized primary amyloidosis and 11 (38%) as secondary manifestation of systemic amyloidosis. In 14 (48%) cases, there was an associated urothelial carcinoma: 5 urothelial carcinoma in situ, 4 low-grade noninvasive papillary urothelial carcinoma, 2 high-grade noninvasive papillary urothelial carcinoma, and 3 high-grade invasive urothelial carcinoma. Associated urothelial carcinoma was present in 4 of 7 patients with systemic amyloidosis and 10 of 18 patients with localized amyloidosis, with the difference not being statistically significant (P = .45). Amyloidosis of the bladder is rare and presents as a mucosal mass or hematuria that may mimic urothelial carcinoma. In this study, we found urothelial carcinoma occurring in 48% of the cases in association with amyloidosis, a finding not previously reported. The relationship of amyloid in the bladder and urothelial carcinoma, although likely not causal, appears to be a unique finding not frequently seen with other solid tumors.	bladder
Validation of vesical imaging reporting and data system for assessing muscle invasion in bladder tumor.	PURPOSE: To retrospectively determine the diagnostic values of vesical imaging reporting and data system (VI-RADS) score for detecting muscle-invasive bladder tumors. METHODS: This study included 297 consecutive patients with 339 tumors who previously diagnosed and subsequently underwent multiparametric MR imaging between January 2015 and March 2019. Two radiologists assessed the scores of muscle-invasive tumors using cutoff values of ≥ 4 and ≥ 3. Cutoff values for VI-RADS scores were estimated from the best operating points of the areas under the receiver operating characteristic curve analyses using the Youden J statistic. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated to assess the utility of VI-RADS for diagnosing muscle-invasive tumors. RESULTS: Inter-observer agreement was excellent for three different MR imaging type at lesion level (k = 0.89 for T2W, k = 0.82 for DW, and k = 0.85 for DCE). At a cutoff value of 4, T2W and DW imaging had a diagnostic accuracy of 79.3% (269/339) for tumor lesions with muscle invasion, which was similar to an overall score of 80.2% (272/339). The overall VI-RAD score showed 80.2% accuracy (272/339), with a cutoff value of ≥ 4, yielding 91.3% sensitivity (85/93), 76.0% specificity (187/246), 83.3% PPV (85/102), and 78.9% NPV (187/237). When we considered an arbitrary overall score of ≥ 3 as the cutoff value, the accuracy was 63.7% (216/339); sensitivity, 94.6% (125/132); specificity, 43.9% (91/207); PPV, 51.6% (125/242); and NPV, 63.7% (91/97). CONCLUSION: VI-RADS has an overall good performance in the diagnosis of muscle-invasive tumors.	bladder
Triacanthine exerts antitumor effects on bladder cancer in vitro and in vivo.	BACKGROUND: Numerous studies have focused on solvent extracts from locust trees (Gleditsia spp.), which contain diverse bioactive components including saponins, flavonoids, and alkaloids. However, because of the undefined nature of such phytochemicals, their clinical application as chemotherapeutic agents has often been limited. PURPOSE: This study aimed to evaluate the anti-oncogenic activity of triacanthine, an alkaloid obtained from Gleditsia triacanthos L. STUDY DESIGN: The anti-oncogenicity of triacanthine in vitro was evaluated via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell-counting kit-8 assay (CCK-8 assay), flow cytometry, imunoblot, migration and invasion assays, zymography, and electrophoretic mobility shift assay in the human bladder carcinoma cell line EJ. The in vivo efficacy of triacanthine was evaluated via oral administration to EJ-xenografted BALB/c nude mice. To identify the side effects of triacanthine, cisplatin was also administered and an acute toxicity test was performed. RESULTS: Triacanthine significantly inhibited EJ cell proliferation (IC(50) 600 µM). Flow cytometry analysis revealed that cells were arrested in the G1 phase, and apoptotic cells accumulated in sub-G1 phase in a dose-dependent manner. Triacanthine inhibited the G1-S transition by deterring complex formation between cyclin-dependent kinases and cyclins, thereby up-regulating cell cycle inhibitors p21WAF1 and p27KIP1. In addition, triacanthine induced a caspase-dependent extrinsic pathway of apoptosis and autophagy. Early responsive kinases, extracellular signal-regulated kinase (ERK) and Janus kinase (JNK) were up-regulated by triacanthine. Triacanthine-mediated inhibition of the migratory and invasive potential of EJ cells was attributed to reduction of matrix metalloproteinase (MMP)-9 due to suppression of binding activities of the transcription factors activator protein (AP)-1, specificity protein (Sp)-1, and nuclear factor (NF)-κB. In an in vivo study, triacanthine significantly limited growth of xenografted tumors. Interestingly, while cisplatin resulted in significant weight loss after a 5-mg/kg dose, triacanthine did not cause weight loss, behavioral abnormalities, altered biochemical parameters, or tissue staining. A single oral dose acute-toxicity test (triacanthine 2,000 mg/kg) produced no adverse cytotoxic effects via blood biochemical tests and tissue-organ staining. CONCLUSION: To our knowledge, this is the first systematic evaluation of the anti-oncogenic activity of triacanthine. Therefore, we believe that our findings may guide the development of novel chemotherapeutic agents for bladder cancers.	bladder
Outcomes for urologic oncology procedures: are there differences between academic and community hospitals?	OBJECTIVE: To compare the rate of hospital-based outcomes including costs, 30-day readmission, mortality, and length of stay in patients who underwent major urologic oncologic procedures in academic and community hospitals. METHODS: We retrospectively reviewed the Vizient Database (Irving, Texas) from September 2014 to December 2017. Vizient includes ~ 97% of academic hospitals (AH) and more than 60 community hospitals (CH). Patients aged ≥ 18 with urologic malignancies who underwent surgical treatment were included. Chi square and Student t tests were used to compare categorical and continuous variables, respectively. RESULTS: We identified a total of 37,628 cases. There were 33,290 (88%) procedures performed in AH and 4330 (12%) in CH. These included prostatectomy (18,540), radical nephrectomy (rNx) 8059, partial nephrectomy (pNx) (5287), radical cystectomy (4421), radical nephroureterectomy (rNu) (1006), and partial cystectomy (321). There were no significant differences in 30-day readmission rates or mortality for any procedure between academic and community hospitals (Table 1), p > 0.05 for all. Length of stay was significantly lower for radical cystectomy and prostatectomy in AH (p < 0.01 for both) and lower for rNx in CH (p = 0.03). The mean direct cost for index admission was significantly higher in AH for rNx, pNx, rNu, and prostatectomy. Case mix index was similar between the community and academic hospitals. CONCLUSION: Despite academic and community hospitals having similar case complexity, direct costs were lower in community hospitals without an associated increase in readmission rates or deaths. Length of stay was shorter for cystectomy in academic centers.	bladder
[Construction of prognostic model and identification of prognostic biomarkers based on the expression of long non-coding RNA in bladder cancer via bioinformatics].	"OBJECTIVE: To construct the prognostic model and identify the prognostic biomarkers based on long non-coding RNA (lncRNA) in bladder cancer. METHODS: The lncRNA expression data and corresponding clinical data of bladder cancer were collected from The Cancer Genome Atlas (TCGA) database. The software Perl and R, and R packages were used for data integration, extraction, analysis and visualization. Detailly, R package ""edgeR"" was utilized to screen differentially expressed lncRNA in bladder cancer tissues compared with the normal bladder samples. The univariate Cox regression and the least absolute shrinkage and selection operator (Lasso) regression were performed to identify key lncRNA that were utilized to construct the prognostic model by the multivariate Cox regression. According to the median value of the risk score, all patients were divided into the high-risk group and low-risk group to perform the Kaplan-Meier (K-M) survival curves, receiver operating characteristic (ROC) curve and C-index, estimating the prognostic power of the prognostic model. In addition, the hazard ratio (HR) and 95% confidence interval (CI) of each key lncRNA were also calculated by the multivariate Cox regression. Moreover, we performed the K-M survival analysis for each significant key lncRNA from the result of the multivariate Cox regression. RESULTS: A total of 691 lncRNA were identified as differentially expressed lncRNA, and 35 lncRNA signatures were initially considered associated with the prognosis of bladder cancer, where in 23 lncRNA were identified as key lncRNA associated with the prognosis. The overall survival time in years of the low-risk group was obviously longer than that of the high-risk group [(2.85±2.72) years vs. (1.58±1.51) years, P<0.001]. The area under the ROC curve (AUC) was 0.813 (3-year survival) and 0.778 (5-year survival) respectively, and the C-index was 0.73. In addition, HR and 95%CI of each key lncRNA were calculated by the multivariate Cox regression and 11 lncRNA were significant. Furthermore, K-M survival analysis revealed the independent prognostic value of 3 lncRNA, including AL589765.1 (P=0.004), AC023824.1 (P=0.022)and PKN2-AS1 (P=0.016). CONCLUSION: The present study successfully constructed the prognostic model based on the expression level of 23 lncRNA and finally identified one protective prognostic biomarker AL589765.1, and two adverse prognostic biomarkers including AC023824.1 and PKN2-AS1 in bladder cancer."	bladder
Rapamycin-upregulated miR-29b promotes mTORC1-hyperactive cell growth in TSC2-deficient cells by downregulating tumor suppressor retinoic acid receptor β (RARβ).	miR-29b has been identified as a rapamycin-induced microRNA (miRNA) in Tsc2-deficient, mTORC1-hyperactive cells. The biological significance of this induction of miR-29b is unknown. We have found that miR-29b acts as an oncogenic miRNA in Tsc2-deficient cells: inhibition of miR-29b suppressed cell proliferation, anchorage-independent cell growth, cell migration, invasion, and the growth of Tsc2-deficient tumors in vivo. Importantly, the combination of miR-29b inhibition with rapamycin treatment further inhibited these tumor-associated cellular processes. To gain insight into the molecular mechanisms by which miR-29b promotes tumorigenesis, we used RNA sequencing to identify the tumor suppressor retinoid receptor beta (RARβ) as a target gene of miR-29b. We found that miR-29b directly targeted the 3'UTR of RARβ. Forced expression of RARβ reversed the effects of miR-29b overexpression in proliferation, migration, and invasion, indicating that it is a critical target. miR-29b expression correlated with low RARβ expression in renal clear cell carcinomas and bladder urothelial carcinomas, tumors associated with TSC gene mutations. We further identified growth family member 4 (ING4) as a novel interacting partner of RARβ. Overexpression of ING4 inhibited the migration and invasion of Tsc2-deficient cells while silencing of ING4 reversed the RARβ-mediated suppression of cell migration and invasion. Taken together, our findings reveal a novel miR-29b/RARβ/ING4 pathway that regulates tumorigenic properties of Tsc2-deficient cells, and that may serve as a potential therapeutic target for TSC, lymphangioleiomyomatosis (LAM), and other mTORC1-hyperactive tumors.	bladder
TGF-β-induced transgelin promotes bladder cancer metastasis by regulating epithelial-mesenchymal transition and invadopodia formation.	BACKGROUND: Metastatic bladder cancer (BLCA) is a lethal disease with an unmet need for study. Transgelin (TAGLN) is an actin-binding protein that affects the dynamics of the actin cytoskeleton indicating its robust potential as a metastasis initiator. Here, we sought to explore the expression pattern of TAGLN and elucidate its specific functioning and mechanisms in BLCA. METHODS: A comprehensive assessment of TAGLN expression in BLCA was performed in three cohorts with a total of 847 patients. The potential effects of TAGLN on BLCA were further determined using clinical genomic analyses that guided the subsequent functional and mechanistic studies. In vitro migration, invasion assays and in vivo metastatic mouse model were performed to explore the biological functions of TAGLN in BLCA cells. Immunofluorescence, western blot and correlation analysis were used to investigate the molecular mechanisms of TAGLN. FINDINGS: TAGLN was highly expressed in BLCA and correlated with advanced prognostic features. TAGLN promoted cell colony formation and cell migration and invasion both in vitro and in vivo by inducing invadopodia formation and epithelial-mesenchymal transition, during which a significant correlation between TAGLN and Slug was observed. The progression-dependent correlation between TGF-β and TAGLN was analysed at both the cellular and tissue levels, while TGF-β-mediated migration was abolished by the suppression of TAGLN. INTERPRETATION: Overall, TAGLN is a promising novel prognosis biomarker of BLCA, and its metastatic mechanisms indicate that TAGLN may represent a novel target agent that can be utilized for the clinical management of invasive and metastatic BLCA. FUND: This work was supported by the National Natural Science Foundation of China [81772703, 81672546, 81602253]; the Natural Science Foundation of Beijing [71772219, 7152146]. and Innovative Fund for Doctoral Students of Peking University Health Science Center (BUM2018BSS002). Funders had no role in the design of the study, data collection, data analysis, interpretation, or the writing of this report.	bladder
Propensity-matched analysis of stage-specific efficacy of adjuvant chemotherapy for bladder cancer.	BACKGROUND: Contemporary randomized controlled trials exploring adjuvant chemotherapy (AC) for bladder cancer (BCa) have yielded inconsistent results due to premature termination and/or poor patient accrual. OBJECTIVE: To compare efficacy of AC vs. observation after radical cystectomy stratified by disease stage in a propensity-matched cohort. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective study that included patients who underwent radical cystectomy for any pT, N0-1, M0 BCa from the National Cancer Data Base (2004-2014). Patients who underwent AC were 1:1 propensity matched with patients who received observation only. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival was assessed with multivariable Cox regression models where adjusted hazard ratios (aHR) and 95% confidence intervals (95% CI) were calculated. RESULTS AND LIMITATIONS: After coarsened exact 1:1 propensity matching, 3,066 patients (AC 1,533; observation 1,533) were included in the analysis. There were no significant differences in patient-, facility-, or tumor-level characteristics among cohorts. Compared with patients who underwent observation, recipients of AC had improved overall survival (aHR 0.67; 95% CI 0.61-0.74). Patients with pT2-4, pN1 disease significantly benefited from AC. Among the pN0 cohort, improved survival from AC was observed only in stages pT3 (aHR 0.67; 95% CI 0.55-0.83) and pT4 (aHR 0.70; 95% CI 0.50-0.98). CONCLUSIONS: AC was associated with improved survival in locally advanced (pT3-4, pN0) and regionally advanced (pT2-4, pN1) chemotherapy-naive BCa.	bladder
Current advances in BCG-unresponsive non-muscle invasive bladder cancer.	Introduction: The current first line therapy for high grade (HG) non-muscle invasive bladder cancer (NMIBC) is intravesical Bacillus Calmette-Guerin (BCG). Patients who recur or progress despite BCG are recommended to undergo radical cystectomy or participate in clinical trials. There is an urgent need for alternative therapies in the BCG-unresponsive NMIBC realm. Areas covered: We queried clinicaltrials.gov and pubmed.gov for current and recently completed early clinical trials pertaining to investigational agents used for the treatment of BCG-unresponsive NMIBC. These included intravesical chemotherapy, immunotherapy, vaccines, gene therapy, viruses, and agents used with novel drug delivery methods. In this article, we discuss the treatment guidelines for non-muscle invasive bladder cancer and therapeutic approaches under investigation in clinical trials. Expert opinion: The FDA is currently allowing single-arm studies as a pathway for approval in BCG-refractory patients with CIS. Although many agents are currently undergoing testing, none have been approved since Valrubicin. Hopefully, we will identify therapies sufficiently effective and durable to achieve FDA approval. Other considerations in this realm include the use of biomarkers in NMIBC to identify patients who will most likely respond to specific interventions. In addition, as systemic agents such as checkpoint inhibitors, are studied further, a multidisciplinary approach may be needed to treat this subset of patients.	bladder